TY - JOUR A1 - Trog, S. A1 - El-Khatib, Ahmed A1 - Beck, S. A1 - Makowski, M. A1 - Jakubowski, Norbert A1 - Linscheid, M. T1 - Complementarity of molecular and elemental mass spectrometric imaging of Gadovist™ in mouse tissues N2 - Drug biodistribution analyses can be considered a key issue in pharmaceutical discovery and development. Here, mass spectrometric imaging can be employed as a powerful tool to investigate distributions of drug compounds in biologically and medically relevant tissue sections. Both matrix-assisted laser desorption ionization–mass spectrometric imaging as molecular method and laser ablation inductively coupled plasma–mass spectrometric imaging as elemental detection method were applied to determine drug distributions in tissue thin sections. Several mouse organs including the heart, kidney, liver, and brain were analyzed with regard to distribution of Gadovist™, a gadolinium-based contrast agent already approved for clinical investigation. This work demonstrated the successful detection and localization of Gadovist™ in several organs. Furthermore, the results gave evidence that gadolinium-based contrast agents in general can be well analyzed by mass spectrometric imaging methods. In conclusion, the combined application of molecular and elemental mass spectrometry could complement each other and thus confirm analytical results or provide additional information. KW - Laser ablation inductively coupled plasma–mass spectrometry imaging (LA-ICP-MSI) KW - Gadolinium-based contrast agents (GBCAs) KW - Matrix-assisted laser desorption ionization–mass spectrometry imaging (MALDI-MSI) PY - 2019 U6 - https://doi.org/10.1007/s00216-018-1477-9 SN - 1618-2642 SN - 1618-2650 VL - 411 IS - 3 SP - 629 EP - 637 PB - Springer AN - OPUS4-47371 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ruhe, L. A1 - Ickert, Stefanie A1 - Beck, S. A1 - Linscheid, M. W. T1 - A new strategy for metal labeling of glycan structures in antibodies N2 - Quantitative analysis of complex proteins is a challenging task in modern bioanalytical chemistry. Commonly available isotope labels are still suffering from limitations and drawbacks, whereas new metal labels open numerous possibilities in mass spectrometric analyses. In this work, we have developed a newmetal labeling strategy to tag glycan structures of proteins, more particularly antibodies. The oligosaccharide glycans were selectively trimmed to the last N-acetylglucosamine to which an artificial azide containing galactose residue was bound. This azide can be used for subsequent cycloaddition of an alkyne. Therefore, we developed a lanthanide-containing macrocyclic reagent to selectively connect to this azido galactose. In summary, the glycan structures of an antibody can be labeled with a metal functionality using this approach. Furthermore, the functionality of the antibodies can be fully maintained by labeling the Fc glycans instead of using labeling reagents that target amino or thiol groups. This approach enables the possibility of using elemental, besides molecular mass spectrometry, for quantitative analyses or imaging experiments of antibodies in complex biological samples. KW - Antibody KW - Metal labeling KW - Glycans KW - DOTA KW - Lanthanide PY - 2018 U6 - https://doi.org/10.1007/s00216-017-0683-1 SN - 1618-2650 SN - 1618-2642 VL - 410 IS - 1 SP - 21 EP - 25 PB - Springer AN - OPUS4-44000 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ickert, Stefanie A1 - Schwaar, Timm A1 - Springer, A. A1 - Grabarics, M. A1 - Riedel, Jens A1 - Beck, S. A1 - Pagel, K. A1 - Linscheid, M. W. T1 - Comparison of the fragmentation behavior of DNA and LNA single strands and duplexes N2 - DNA and locked nucleic acid (LNA) were characterized as single strands, as well as double stranded DNA-DNA duplexes and DNA-LNA hybrids using tandem mass spectrometry with collision-induced dissociation. Additionally, ion mobility spectrometry was carried out on selected species. Oligonucleotide duplexes of different sequences – bearing mismatch positions and abasic sites of complementary DNA 15-mers – were investigated to unravel general trends in their stability in the gas phase. Single stranded LNA oligonucleotides were also investigated with respect to their gas phase behavior and fragmentation upon collision-induced dissociation. In contrast to the collision-induced dissociation of DNA, almost no base loss was observed for LNAs. Here, backbone cleavages were the dominant dissociation pathways. This finding was further underlined by the need for higher activation energies. Base losses from the LNA strand were also absent in fragmentation experiments of the investigated DNA-LNA hybrid duplexes. While DNA-DNA duplexes dissociated easily into single stranded fragments, the high stability of DNA-LNA hybrids resulted in predominant fragmentation of the DNA part rather than the LNA, while base losses were only observed from the DNA single strand of the hybrid. KW - Oligonucleotide fragmentation KW - Locked nucleic acids KW - Collision induced dissociation (CID) KW - Double strands KW - Ion mobility spectrometry PY - 2019 U6 - https://doi.org/10.1002/jms.4344 VL - 54 IS - 5 SP - 402 EP - 411 PB - Wiley AN - OPUS4-47485 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ickert, Stefanie A1 - Riedel, Jens A1 - Beck, S. A1 - Linscheid, M. W. T1 - Negative nucleotide ions as sensitive probes for energy specificity in collision‐induced fragmentation in mass spectrometry N2 - Rationale: The most commonly used fragmentation methods in tandem mass spectrometry (MS/MS) are collision‐induced dissociation (CID) and higher energy collisional dissociation (HCD). While in CID the preselected ions in the trap are resonantly (and m/z exclusively) excited, in HCD the entire m/z range experiences the dissociative acceleration. The different excitation is reflected in different fragment distributions. Methods: As a test‐bed for particularly pronounced fragmentation specificity, here MS/MS experiments on several 4‐mer oligonucleotides were conducted employing both collision methods and the results were thoroughly compared. Oligonucleotides are shown to be sensitive probes to subtle changes, especially in the negative ion mode. A detailed analysis of these differences reveals insight into the dissociation mechanics. Results: Thedifferencesarerepresentedinheat‐maps,whichallowforadirectvisualinspection oflargeamountsofdata.Inthesefalsecolourrepresentationsthe,sometimessubtle,changesinthe individual dissociation product distributions become distinct. Another advantage of these graphic plots can be found in the formation of systematic patterns. These patterns reflect trends in dissociation specificity which allow for the formulation of general rules in fragmentation behavior. Conclusions: Instruments equipped with two different excitation schemes for MS/MS are today widely available. Nonetheless, direct comparisons between the individual results are scarcely made. Such comparative studies bear a powerful analytical potential to elucidate fragmentation reaction mechanism. KW - DNA KW - Tandem MS KW - HCD KW - CID PY - 2018 U6 - https://doi.org/10.1002/rcm.8062 SN - 0951-4198 SN - 1097-0231 VL - 32 IS - 7 SP - 597 EP - 603 PB - Wiley & Sons, Ltd. AN - OPUS4-44430 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ickert, Stefanie A1 - Hofmann, J. A1 - Riedel, Jens A1 - Beck, S. A1 - Pagel, K. A1 - Linscheid, M. W. T1 - Charge-induced geometrical reorganization of DNA oligonucleotides studied by tandem mass spectrometry and ion mobility N2 - Mass spectrometry is applied as a tool for the elucidation of molecular structures. This premises that gas-phase structures reflect the original geometry of the analytes, while it requires a thorough understanding and investigation of the forces controlling and affecting the gas-phase structures. However, only little is known about conformational changes of oligonucleotides in the gas phase. In this study, a series of multiply charged DNA oligonucleotides (n¼15–40) has been subjected to a comprehensive tandem mass spectrometric study to unravel transitions between different ionic gas-phase structures. The nucleobase sequence and the chain length were varied to gain insights into their influence on the geometrical oligonucleotide organization. Altogether, 23 oligonucleotides were analyzed using collision-induced fragmentation. All sequences showed comparable correlation regarding the characteristic collision energy. This value that is also a measure for stability, strongly correlates with the net charge density of the precursor ions. With decreasing charge of the oligonucleotides, an increase in the fragmentation energy was observed. At a distinct charge density, a deviation from linearity was observed for all studied species, indicating a structural reorganization. To corroborate the proposed geometrical change, collisional cross-sections of the oligonucleotides at different charge states were determined using ion mobility-mass spectrometry. The results clearly indicate that an increase in charge density and thus Coulomb repulsion results in the transition from a folded, compact form to elongated structures of the precursor ions. Our data show this structural transition to depend mainly on the charge density, whereas sequence and size do not have an influence. KW - Ion mobility KW - Collision-induced dissociation KW - Mass spectrometry KW - Oligonucleotide KW - Fragmentation KW - Tandem-MS PY - 2018 U6 - https://doi.org/10.1177/1469066717746896 SN - 1469-0667 SN - 1751-6838 VL - 24 IS - 2 SP - 225 EP - 230 PB - Sage AN - OPUS4-44429 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ickert, Stefanie A1 - Beck, S. A1 - Linscheid, M. A1 - Riedel, Jens T1 - VUV Photodissociation Induced by a Deuterium Lamp in an Ion Trap N2 - Tandem mass spectrometry represents an important analytical tool to unravel molecular structures and to study the gas-phase behavior of organic molecules. Besides commonly used methods like collision-induced dissociation and electron capture or transfer dissociation, new ultraviolet light–based techniques have the potential to synergistically add to the activation methods. Here, we present a new simple, yet robust, experimental design for polychromatic activation of trapped ions using the 115–160 nm output of a commercially available deuterium lamp. The resulting continuous dissociative excitation with photons of a wide energy range from 7.7 to 10.8 eV is studied for a comprehensive set of analyte classes in both positive and negative ion modes. While being simple, affordable, compact, and of low maintenance, the new setup initiates fragmentation of most precursor ions via their known dissociation pathways. Additionally, some new fragmentation patterns were discovered. Especially, electron loss and electron capture reactions with subsequent fragmentations were observed. For oligonucleotides, peptides, carbohydrates, and organic dyes, in comparison to collision-induced dissociation, a significantly wider fragment distribution was obtained, resulting in an information increase. Since the individual photons carry enough energy to post-ionize the nascent fragments, a permanent vacuum ultraviolet light exposure inside the ion trap potentially goes along with a general increase in detection capability. KW - Fragmentation activation KW - Vacuum ultraviolet (VUV) light KW - Mass spectrometry KW - Tandem MS PY - 2019 U6 - https://doi.org/10.1007/s13361-019-02282-8 SN - 1044-0305 VL - 30 IS - 10 SP - 2114 EP - 2122 PB - Springer Nature CY - Heidelberg AN - OPUS4-48756 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - El-Khatib, A. H. A1 - Radbruch, H. A1 - Trog, S. A1 - Neumann, B. A1 - Paul, F. A1 - Koch, A. A1 - Linscheid, M. W. A1 - Jakubowski, Norbert A1 - Schellenberger, E. T1 - Gadolinium in human brain sections and colocalization with other elements N2 - Recent recommendations by the Food and Drug Administration1 and the European Medicines Agency2 are to limit the clinical use of linear gadolinium-based contrast agents (GBCAs) due to convincing evidence of deposition in tissues. Macrocyclic GBCA continued to be considered safe, provided that patients have normal renal function. To date, given the low sensitivity of conventional MRI, there has been a debate about the signal increase following the injections of a macrocyclic GBCA. KW - Gadolinium PY - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-471309 SN - 2332-7812 VL - 6 IS - 1 SP - e515, 1 EP - 3 PB - American Academy of Neurology AN - OPUS4-47130 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -